BACKGROUND It is challenging to distinguish intestinal tuberculosis from Crohn’s disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in ge...BACKGROUND It is challenging to distinguish intestinal tuberculosis from Crohn’s disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in genes involved in the interleukin (IL)- 23/IL-17 axis may affect intestinal mucosal immunity by affecting the differentiation of Th17 cells. AIM To investigate the specific single-nucleotide polymorphisms (SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn's disease. METHODS We analysed 133 patients with intestinal tuberculosis, 128 with Crohn’s disease, and 500 normal controls. DNA was extracted from paraffin-embedded specimens or whole blood. Four SNPs in the IL23/Th17 axis (IL22 rs2227473, IL1β rs1143627, TGFβ rs4803455, and IL17 rs8193036) were genotyped with TaqMan assays. The transcriptional activity levels of different genotypes of rs2227473 were detected by dual luciferase reporter gene assay. The expression of IL-22R1 in different intestinal diseases was detected by immunohistochemistry. RESULTS The A allele frequency of rs2227473 (P = 0.030, odds ratio = 0.60, 95% confidence interval: 0.37-0.95) showed an abnormal distribution between intestinal tuberculosis and healthy controls. The presence of the A allele was associated with a higher IL-22 transcriptional activity (P < 0.05). In addition, IL-22R1 was expressed in intestinal lymphoid tissues, especially under conditions of intestinal tuberculosis, and highly expressed in macrophage-derived Langhans giant cells. The results of immunohistochemistry showed that the expression of IL-22R1 in patients with Crohn's disease and intestinal tuberculosis was significantly higher than that in patients with intestinal polyps and colon cancer (P < 0.01). CONCLUSION High IL-22 expression seems to be a protective factor for intestinal tuberculosis. IL-22R1 is expressed in Langhans giant cells, suggesting that the IL-22/IL-22R1 system links adaptive and innate immunity.展开更多
AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained fr...AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p- STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting. RESULTS:Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated.CONCLUSION:IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC.展开更多
INTRODUCTIONThe increased expression of ICAM-1 on a widerange of cells and in the sera of patients withmalignancies, chronic liver diseases andinflammation diseases has been described since thelate 1980s[1-22]. Recent...INTRODUCTIONThe increased expression of ICAM-1 on a widerange of cells and in the sera of patients withmalignancies, chronic liver diseases andinflammation diseases has been described since thelate 1980s[1-22]. Recently rapid progress in studieson expression of ICAM-1 in patients withhepatocellular carcinoma ( HCC ) have beenachieved, including clinical and experimentalresearches[23-31].展开更多
Many studies have shown that(5R)-5-hydroxytriptolide is the optimal modified analogue of triptolide, possessing comparable immunosuppressive activity but much lower cytotoxicity than triptolide. Whether(5R)-5-hydroxyt...Many studies have shown that(5R)-5-hydroxytriptolide is the optimal modified analogue of triptolide, possessing comparable immunosuppressive activity but much lower cytotoxicity than triptolide. Whether(5R)-5-hydroxytriptolide has preventive effects on neuroinflammation is unclear. This study was designed to pretreat primary astrocytes from the brains of neonatal Sprague-Dawley rats with 20, 100 and 500 nM(5R)-5-hydroxytriptolide for 1 hour before establishing an in vitro neuroinflammation model with 1.0 μg/mL lipopolysaccharide for 24 hours. The generation of nitric oxide was detected by Griess reagents. Astrocyte marker glial fibrillary acidic protein was measured by immunohistochemical staining. The levels of tumor necrosis factor-α and interleukin-1β in the culture supernatant were assayed by enzyme linked immunosorbent assay. Nuclear factor-κB/p65 expression was examined by immunofluorescence staining. The phosphorylation of inhibitor of nuclear factor IκB-α and the location of nuclear factor-κB/P65 were determined using western blot assay. Our data revealed that(5R)-5-hydroxytriptolide inhibited the generation of nitric oxide, tumor necrosis factor-α and interleukin-1β from primary astrocytes activated by lipopolysaccharide, decreased the positive reaction intensity of glial fibrillary acidic protein, reduced the expression of tumor necrosis factor alpha and interleukin-1β in culture supernatant, inhibited the phosphorylation of IκB-α and the translocation of nuclear factor-κB/P65 to the nucleus. These results have confirmed that(5R)-5-hydroxytriptolide inhibits lipopolysaccharide-induced glial inflammatory response and provides cytological experimental data for(5R)-5-hydroxytriptolide in the treatment of neurodegenerative diseases.展开更多
空气源热泵热水机组(Air-Source Heat Pump Hot Water Unit)是当今世界上开拓利用新能源最好的设备之一,是继锅炉、燃气热水器、电热水器和太阳能热水器之后的新一代热水制取装置。对于R22冷媒T1转子压缩机搭载小型家用空气源热泵热水...空气源热泵热水机组(Air-Source Heat Pump Hot Water Unit)是当今世界上开拓利用新能源最好的设备之一,是继锅炉、燃气热水器、电热水器和太阳能热水器之后的新一代热水制取装置。对于R22冷媒T1转子压缩机搭载小型家用空气源热泵热水器应用可靠性评价确认,实验结果表明转子空调压缩机可以满足出水终温为55℃使用条件热泵热水器应用以及可靠性方面要求。展开更多
Background:In Type 1 diabetes,the insulin-producingβ-cells within the pancreatic islets of Langerhans are destroyed.We showed previously that immunotherapy with Bacillus Calmette-Guerin(BCG)or complete Freund’s adju...Background:In Type 1 diabetes,the insulin-producingβ-cells within the pancreatic islets of Langerhans are destroyed.We showed previously that immunotherapy with Bacillus Calmette-Guerin(BCG)or complete Freund’s adjuvant(CFA)of non-obese diabetic(NOD)mice can prevent disease process and pancreaticβ-cell loss.This was associated with increased islet Regenerating(Reg)genes expression,and elevated IL-22-producing Th17 T-cells in the pancreas.Results:We hypothesized that IL-22 was responsible for the increased Reg gene expression in the pancreas.We therefore quantified the Reg1,Reg2,and Reg3δ(INGAP)mRNA expression in isolated pre-diabetic NOD islets treated with IL-22.We measured IL-22,and IL-22 receptor(R)-αmRNA expression in the pancreas and spleen of pre-diabetic and diabetic NOD mice.Our results showed:1)Reg1 and Reg2 mRNA abundance to be significantly increased in IL-22-treated islets in vitro;2)IL-22 mRNA expression in the pre-diabetic mouse pancreas increased with time following CFA treatment;3)a reduced expression of IL-22Rαfollowing CFA treatment;4)a down-regulation in Reg1 and Reg2 mRNA expression in the pancreas of pre-diabetic mice injected with an IL-22 neutralizing antibody;and 5)an increased isletβ-cell DNA synthesis in vitro in the presence of IL-22.Conclusions:We conclude that IL-22 may contribute to the regeneration ofβ-cells by up-regulating Regenerating Reg1 and Reg2 genes in the islets.展开更多
基金Supported by Key R&D Plan of Science and Technology Department of Jiangxi Province,No.20171BBG70087
文摘BACKGROUND It is challenging to distinguish intestinal tuberculosis from Crohn’s disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in genes involved in the interleukin (IL)- 23/IL-17 axis may affect intestinal mucosal immunity by affecting the differentiation of Th17 cells. AIM To investigate the specific single-nucleotide polymorphisms (SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn's disease. METHODS We analysed 133 patients with intestinal tuberculosis, 128 with Crohn’s disease, and 500 normal controls. DNA was extracted from paraffin-embedded specimens or whole blood. Four SNPs in the IL23/Th17 axis (IL22 rs2227473, IL1β rs1143627, TGFβ rs4803455, and IL17 rs8193036) were genotyped with TaqMan assays. The transcriptional activity levels of different genotypes of rs2227473 were detected by dual luciferase reporter gene assay. The expression of IL-22R1 in different intestinal diseases was detected by immunohistochemistry. RESULTS The A allele frequency of rs2227473 (P = 0.030, odds ratio = 0.60, 95% confidence interval: 0.37-0.95) showed an abnormal distribution between intestinal tuberculosis and healthy controls. The presence of the A allele was associated with a higher IL-22 transcriptional activity (P < 0.05). In addition, IL-22R1 was expressed in intestinal lymphoid tissues, especially under conditions of intestinal tuberculosis, and highly expressed in macrophage-derived Langhans giant cells. The results of immunohistochemistry showed that the expression of IL-22R1 in patients with Crohn's disease and intestinal tuberculosis was significantly higher than that in patients with intestinal polyps and colon cancer (P < 0.01). CONCLUSION High IL-22 expression seems to be a protective factor for intestinal tuberculosis. IL-22R1 is expressed in Langhans giant cells, suggesting that the IL-22/IL-22R1 system links adaptive and innate immunity.
基金Supported by National Natural Science Foundation of China,No.81072692Natural Science Foundation of Jiangsu Higher Education Institutions of China,No.10KJB320007
文摘AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p- STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting. RESULTS:Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated.CONCLUSION:IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC.
基金Supported by the grant from the Guangxi ScienceTechnology Committee, No. 9811003
文摘INTRODUCTIONThe increased expression of ICAM-1 on a widerange of cells and in the sera of patients withmalignancies, chronic liver diseases andinflammation diseases has been described since thelate 1980s[1-22]. Recently rapid progress in studieson expression of ICAM-1 in patients withhepatocellular carcinoma ( HCC ) have beenachieved, including clinical and experimentalresearches[23-31].
基金supported by the National Natural Science Foundation of China,No.81402932(to YQC)
文摘Many studies have shown that(5R)-5-hydroxytriptolide is the optimal modified analogue of triptolide, possessing comparable immunosuppressive activity but much lower cytotoxicity than triptolide. Whether(5R)-5-hydroxytriptolide has preventive effects on neuroinflammation is unclear. This study was designed to pretreat primary astrocytes from the brains of neonatal Sprague-Dawley rats with 20, 100 and 500 nM(5R)-5-hydroxytriptolide for 1 hour before establishing an in vitro neuroinflammation model with 1.0 μg/mL lipopolysaccharide for 24 hours. The generation of nitric oxide was detected by Griess reagents. Astrocyte marker glial fibrillary acidic protein was measured by immunohistochemical staining. The levels of tumor necrosis factor-α and interleukin-1β in the culture supernatant were assayed by enzyme linked immunosorbent assay. Nuclear factor-κB/p65 expression was examined by immunofluorescence staining. The phosphorylation of inhibitor of nuclear factor IκB-α and the location of nuclear factor-κB/P65 were determined using western blot assay. Our data revealed that(5R)-5-hydroxytriptolide inhibited the generation of nitric oxide, tumor necrosis factor-α and interleukin-1β from primary astrocytes activated by lipopolysaccharide, decreased the positive reaction intensity of glial fibrillary acidic protein, reduced the expression of tumor necrosis factor alpha and interleukin-1β in culture supernatant, inhibited the phosphorylation of IκB-α and the translocation of nuclear factor-κB/P65 to the nucleus. These results have confirmed that(5R)-5-hydroxytriptolide inhibits lipopolysaccharide-induced glial inflammatory response and provides cytological experimental data for(5R)-5-hydroxytriptolide in the treatment of neurodegenerative diseases.
文摘空气源热泵热水机组(Air-Source Heat Pump Hot Water Unit)是当今世界上开拓利用新能源最好的设备之一,是继锅炉、燃气热水器、电热水器和太阳能热水器之后的新一代热水制取装置。对于R22冷媒T1转子压缩机搭载小型家用空气源热泵热水器应用可靠性评价确认,实验结果表明转子空调压缩机可以满足出水终温为55℃使用条件热泵热水器应用以及可靠性方面要求。
基金We thank Ms.Brenda Strutt and Jessica Hill for technical help and Dr.Margery Ma from Pfizer,Cambridge,MA for anti-IL-22 antibody.We also thank Dr.Kathleen Hill,Dr.Alexander Timoshenko and Morgan Kleiber for assistance in experimental design and interpretation of the data.This work was supported by grants from the Canadian Institutes of Health Research(CIHR).
文摘Background:In Type 1 diabetes,the insulin-producingβ-cells within the pancreatic islets of Langerhans are destroyed.We showed previously that immunotherapy with Bacillus Calmette-Guerin(BCG)or complete Freund’s adjuvant(CFA)of non-obese diabetic(NOD)mice can prevent disease process and pancreaticβ-cell loss.This was associated with increased islet Regenerating(Reg)genes expression,and elevated IL-22-producing Th17 T-cells in the pancreas.Results:We hypothesized that IL-22 was responsible for the increased Reg gene expression in the pancreas.We therefore quantified the Reg1,Reg2,and Reg3δ(INGAP)mRNA expression in isolated pre-diabetic NOD islets treated with IL-22.We measured IL-22,and IL-22 receptor(R)-αmRNA expression in the pancreas and spleen of pre-diabetic and diabetic NOD mice.Our results showed:1)Reg1 and Reg2 mRNA abundance to be significantly increased in IL-22-treated islets in vitro;2)IL-22 mRNA expression in the pre-diabetic mouse pancreas increased with time following CFA treatment;3)a reduced expression of IL-22Rαfollowing CFA treatment;4)a down-regulation in Reg1 and Reg2 mRNA expression in the pancreas of pre-diabetic mice injected with an IL-22 neutralizing antibody;and 5)an increased isletβ-cell DNA synthesis in vitro in the presence of IL-22.Conclusions:We conclude that IL-22 may contribute to the regeneration ofβ-cells by up-regulating Regenerating Reg1 and Reg2 genes in the islets.
